Recent technological advances have made it clear that sugar chains are involved in a variety of life processes and the importance of sugar-chain compounds has been even more strongly recognized. One method of synthesizing sugar-chain compounds is through an enzyme-catalyzed glycosylation reaction. Glycosylation using a sugar oxazoline derivative as the sugar donor among the enzyme-catalyzed glycosylation reactions is a very useful method of synthesizing glycosides because the glycosylation reaction is an addition reaction and advances without any accompanying elimination of acid, water, or the like. Compounds having an added sugar chain are useful for various purposes, for example, as a bioactive oligosaccharide, carrier of a drug delivery system, surfactant, glycopharmaceutical, glycopeptide, glycoprotein, glycopolymer, and the like.
Sugar derivatives having an activated anomer carbon are known as sugar donors of glycosylation reactions using a glycohydrolase. Sugar oxazoline derivatives among them are a useful substrate as a sugar donor having no leaving groups. However, conventional methods of synthesizing sugar oxazoline derivatives require the use of an organic solvent and include multiple steps, including the protection and deprotection of the hydroxyl groups present in the sugar [S. Shoda et al., Helv. Chim. Acta, 85, 3919 (2002) (Non-patent Document 1)]. The synthesis of oxazoline derivatives of oligosaccharides is particularly difficult [Bing Li et al., J. Am. Chem. Soc., 127, 9692 (2005) (Non-patent Document 2)] and is seldom performed today. Conventional methods of synthesizing sugar oxazoline derivatives are also known, as in JP Kokai 9-3088 (Patent Document 1) and JP Kokai 2003-12683 (Patent Document 2). Such conventional chemical synthesis methods involve a complex procedure and are difficult to apply to long sugar chains because they require multiple steps such as protection and deprotection of hydroxyl groups. The development of a technique to simply and moderately synthesize sugar oxazoline derivatives without using steps such as protection and deprotection is consequently desired in sugar chain synthesis
From this viewpoint, a method of synthesizing a sugar oxazoline derivative from an unprotected sugar in one step using a water-soluble carbodiimide as a dehydrating agent was developed [J. Kadokawa et al., Heterocycles, 63(7), (2004), pp. 1531-1535 (Non-patent Document 3) and H. Gyakushi et al., Abstracts of the Second Tohoku University Bioscience Symposium, “One-step synthesis of sugar oxazoline derivatives using a water-soluble carbodiimide,” May 2005 (Non-patent Document 4)]. A method of direct synthesis of sugar oxazoline derivatives from unprotected sugars in an aqueous solvent using a triazine derivative as a dehydrating agent has also been developed [55th Society of Polymer Science Meeting, Title: “One-pot polymerization reaction of non-protected sugars by dehydrative condensing agent-enzyme system,” Authors: M. Noguchi, T. Misawa, M. Ishihara, A. Kobayashi, S. Shoda, Journal name: Polymer Preprints, Japan Vol. 55, No. 2 (2006), pp. 4826 (Non-patent Document 5); 2006 Society of Polymer Science Tohoku Branch Research Publications Meeting, Title: “One-pot synthesis of polysaccharides from non-protected sugars by employing enzymatic polymerization reaction,” Authors: M. Noguchi, T. Misawa, M. Ishihara, A. Kobayashi, S. Shoda, Journal name: Abstracts of the 2006 Society of Polymer Science Tohoku Branch Research Publications Meeting, pp. 21 (Non-patent Document 6); H. Gyakushi et al., Abstracts of the Third Tohoku University Bioscience Symposium, “One-pot glycosylation of non-protected sugars,” May 2006 (Non-patent Document 7)].    Patent Document 1: JP Kokai 9-3088 (JP, 9-3088, A1 (1997))    Patent Document 2: JP Kokai 2003-12683 (JP, 2003-12683, A1)    Non-patent Document 1: S. Shoda et al., Helv. Chim. Acta, 85, 3919 (2002)    Non-patent Document 2: Bing Li et al., J. Am. Chem. Soc., 127, 9692 (2005)    Non-patent Document 3: J. Kadokawa, M. Mito, S. Takahashi, M. Noguchi, S. Shoda, “Direct Conversion of 2-Acetamido-2-Deoxysugars to 1,2-Oxazoline Derivatives by Dehydrative Cyclization,” Heterocycles, 63(7), (2004), pp. 1531-1535    Non-patent Document 4: H. Gyakushi, S. Takahashi, M. Shiratori, M. Noguchi, A. Kobayashi, S. Shoda, Abstracts of the Second Tohoku University Bioscience Symposium, “One-step synthesis of sugar oxazoline derivatives using a water-soluble carbodiimide,” May 2005.    Non-patent Document 5: 55th Society of Polymer Science Meeting,
Title: “One-pot polymerization reaction of non-protected sugars by dehydrative condensing agent-enzyme system,” Authors: M. Noguchi, T. Misawa, M. Ishihara, A. Kobayashi, S. Shoda, Journal name: Polymer Preprints, Japan Vol. 55, No. 2 (2006), p. 4826    Non-patent Document 6: 2006 Society of Polymer Science Tohoku Branch Research Publications Meeting, Title: “One-pot synthesis of polysaccharides from non-protected sugars by employing enzymatic polymerization reaction,” Authors: M. Noguchi, T. Misawa, M. Ishihara, A. Kobayashi, S. Shoda, Journal name: Abstracts of the 2006 Society of Polymer Science Tohoku Branch Research Publications Meeting, pp. 21    Non-patent Document 7: H. Gyakushi et al., Abstracts of the Third Tohoku University Bioscience Symposium, “One-pot glycosylation of non-protected sugars,” May 2006